Genetic study of Common Hereditary Bowel Cancers in Hispania and the Americas

Colorectal cancer (CRC) is common in both sexes, has relatively poor outcome and has no major avoidable risk factor. Recent studies have shown that common inherited single nucleotide polymorphisms (SNPs) can increase cancer risk. We have shown CRC risk to be associated with SNPs on chromosomes 8q24.21, 15q14 and 8q21. These variants account for <5% of the genetic risk of CRC, but will be very important when their effects are added to those of other, as-yet undetected CRC SNPs. A few genome-wide association studies (GWASs) based on populations of European descent are trying to identify the remaining common CRC genes. Evidence suggests that these studies will not be large enough on their own to detect all CRC SNPs, as: relative risks associated with most SNPs are modest; some disease alleles are rare, at least in Europe; and many variants may lie outside conventional gene boundaries or haplotype blocks. The admixed LA population provides an exciting opportunity to identify new CRC genes that are more tractable to detection in LA, or have been missed by chance in European studies. We shall undertake a combined GWAS and admixture mapping study for CRC predisposition genes in 6,000 LA cases and 6,000 controls. We shall test the disease-associated variants in 3,500 cases and 3,500 controls from Europe. We aim primarily to detect SNPs with effects in both LA and Europe, but also SNPs with effects specific to LA. Eventually, we aim to develop a polymorphism panel for predicting the risk of CRC in the general population, so that those at increased risk can be offered effective measures to prevent cancer. CRC is increasing in frequency in LA and prognosis is poorer than in Europe. We shall use our project as a focus for education about CRC, especially in LA. The study will also provide training for young LA researchers. Our work will provide a direct benefit to medical science and the populations of LA and Europe.